Project Abstract There is strong evidence of human immunodeficiency virus infected (HIV+) children being more at risk for hearing loss. Identification of permanent hearing loss is important because hearing loss can impact speech and language development in children. The primary goal is to collect hearing sensitivity data from South African children who were perinatally infected with HIV (PHIV+). Children will be recruited from two ongoing studies in Cape Town, South Africa: the Children with HIV Early Antiretroviral Therapy (CHER) trial and the P1104s study of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT). Hearing data will be obtained in PHIV+, HIV-exposed but uninfected (PHEU), and HIV-unexposed and uninfected (HU) children using a hearing examination protocol. The hearing protocol includes: 1) otoscopy, to evaluate the ear canal and tympanic membrane; 2) tympanometry, to evaluate middle-ear function; 3) pure-tone air- and bone-conduction audiometry, speech audiometry, dichotic digits testing (together with measures of neurocognitive function), to evaluate the entire auditory system; 4) distortion product otoacoustic emissions (DPOAEs), to evaluate cochlear function within the inner ear; and 5) auditory brainstem responses (ABRs), to evaluate auditory neural function to the level of the brainstem. Advanced multimodal neuroimaging techniques, including structural magnetic resonance imaging (MRI) for morphometry, task based and resting state functional MRI (FMRI) to assess auditory cortex function and network connectivity, and diffusion tensor imaging, will be used to evaluate the effects of HIV on the different components of the central auditory system in a comprehensive way. Speech audiometry measures will also be used to determine the impact of HIV on communication. Using DPOAEs, ABRs, and imaging in one protocol will allow for an examination of how specific auditory stimuli are processed from within the cochlea, along the auditory neural pathway to the brainstem, and finally to targeted components of the auditory cortex. These measures will contribute to a better understanding as to which portions of the auditory system are more vulnerable to HIV. There are two advantages of this proposal. First there is an existing collaboration with researchers in Cape Town and there is a new collaboration with neuroimaging experts in Cape Town; the continued support from CHER and P1104s researchers will allow for access to extensive demographic data and HIV disease and treatment data since childhood. Second, the extensive hearing protocol paired with an extensive neuroimaging protocol will provide the first of its kind data in HIV-infected children. These data will impact both the HIV and hearing literatures.